A Fatal Case of Life-Threatening Interstitial Pneumonitis Induced by Everolimus for Metastatic Renal Cell Carcinoma: A Comment about the Increased Risk of Interstitial Lung Disease in Japanese

We describe an 81-year-old woman with metastatic renal cell carcinoma who did not recover from life-threatening interstitial pneumonitis induced by everolimus therapy. She received everolimus due to disease progression after sunitinib, but 2 months after starting everolimus treatment, she visited the emergency department after developing a sudden fever and dyspnea. Chest CT revealed diffuse ground-glass opacities, thickening of the interlobular septa, and consolidation throughout both lung fields. The diagnosis was surmised to be everolimus-induced interstitial pneumonitis. Everolimus administration was stopped and 3 courses of steroid pulse therapy were administered, along with intensive care, but the patient died due to rapid respiratory failure.

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Successful Response to Nivolumab Plus Ipilimumab Therapy in a Hemodialysis Patient With Metastatic Renal Cell Carcinoma

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10028 ◽

2021 ◽

Vol 1 (3) ◽

pp. 207-211

Author(s):

HIROSHI MASUDA ◽

KOSUKE MIKAMI ◽

KOTARO OTSUKA ◽

KYOKUSIN HOU ◽

TAKAHITO SUYAMA ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Hemodialysis Patient ◽

Pulse Therapy ◽

Hemodialysis Patients ◽

Combination Immunotherapy ◽

Efficacy And Safety ◽

Steroid Pulse

Background/Aim: There are few reports about the administration of nivolumab plus ipilimumab to hemodialysis patients and their efficacy and safety have not been established yet. Case Report: A 74-year-old male, who was receiving hemodialysis, was presented with metastatic renal cell carcinoma (mRCC). Two years later, more metastases were found, hence, immunotherapy involving nivolumab plus ipilimumab was initiated. After two doses of immunotherapy, interstitial pneumonia was observed. Thus, steroid pulse therapy was administered immediately. Subsequently, computed tomography (CT) findings and symptoms improved markedly. One month later, a CT scan showed a nodular shadow and an air cavity. A fungal infection was strongly suspected, so an antifungal drug was administered. Conclusion: Combination immunotherapy with nivolumab plus ipilimumab was demonstrated to be effective in a hemodialysis patient with mRCC.

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Bullous pemphigoid associated with the 480-mg nivolumab dose in a patient with metastatic renal cell carcinoma

Immunotherapy ◽

10.2217/imt-2019-0027 ◽

2019 ◽

Vol 11 (14) ◽

pp. 1187-1192 ◽

Cited By ~ 1

Author(s):

Amruth Ratnakar Palla ◽

Emily Smith ◽

Donald Doll

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Bullous Pemphigoid ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Second Line Therapy ◽

Line Therapy ◽

Increased Risk ◽

The Us ◽

Us Fda

The US FDA has recently approved an updated nivolumab dosing schedule, a single 480 mg iv. dose every 4 weeks [ 1 ], across all its previously approved indications, including second-line therapy for metastatic renal cell carcinoma. As this regimen is still in its infancy, we have not yet observed significant differences in immune-related toxicities and have not yet identified clinical characteristics which would predict intolerance and increased risk for complications. Herein, we present a patient with metastatic renal cell carcinoma who developed bullous pemphigoid after a single 480 mg iv. dose of nivolumab after previously tolerating a 240 mg biweekly dose for 2 years.

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Interstitial lung diseases during treatment with sunitinib or mTOR inhibitors in metastatic renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.420 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 420-420

Author(s):

Philipp Ivanyi ◽

Thomas Fuehner ◽

Meike Adam ◽

Christian Eichelberg ◽

Edwin Herrmann ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Dose Reduction ◽

Metastatic Renal Cell Carcinoma ◽

Targeted Therapies ◽

Renal Cell ◽

Pulmonary Function Tests ◽

Mtor Inhibitors ◽

Treatment Withdrawal ◽

Steroid Pulse

420 Background: Targeted therapies are the mainstay for metastatic renal cell carcinoma (mRCC) treatment. Interstitial lung disease (ILD) represents an adverse event (AE) of such therapies while its incidence and management is poorly defined. Here, the experience on ILD with targeted agents in mRCC is reported. Methods: Retrospective analysis of mRCC patients receiving sunitinib, everolimus, or temsirolimus at three German tertiary centers between January 2006 and August 2009 was performed, accessing ILD incidence, management, and outcomes. Results: In total 26 ILD patients were identified out of 306 mRCC patients (8.5%) treated with targeted therapies. Median treatment duration to ILD diagnosis was 3.8 (range 0.98-21.5) months. ILD occurred in 6 of 204 sunitinib treated patients (2.9%), and in 20 of 102 mTOR inhibitor (mTORi) treated patients (19.6%). Cough represents the predominant symptom (69.2%, n=18). Chest CTs revealed 4 patterns: interstitial (n=13), nodular (n=3), ground glass opacities (n=8), or complex patterns (n=2). Pulmonary function tests (PFT) illustrates frequently a restrictive disorder (n=9), often accompanied by a diminished diffusion capacity (n=8). In 53.8% (n=14) a bronchoscopy with broncho-alveolar-lavage (BAL) was performed (lymphocytic cellularity n=6, eosinophilic cellularity n=4). Dose reduction (42.3%, n=11), temporary interruption (46.2%, n=12), or treatment withdrawal (53.8%, n=14) occurred frequently. Nine patients (34.6%) received steroids. Continuation of targeted therapies was maintained in 65.4% (n=17). No patient died from ILD. Conclusions: ILD represents a frequent AE with targeted therapies and also occurs in sunitinib treated patients. For diagnosis of ILD chest CTs are mandatory, whereas PFT and BALs are important subsidiary tools. Clinical relevance of ILD may vary and management of ILD ranges from watch and wait to termination of treatment and steroid pulse therapy. Severe complaints were more frequently associated with eosinophilic BAL, often required an aggressive treatment. However, in most patients, temporary interruption and/or dose reduction with subsequent continuation of targeted therapy remain sufficient to manage ILD.

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Everolimus-Induced Interstitial Pneumonitis in a Patient with Metastatic Renal Cell Carcinoma: a Case Report

Korean Journal of Medicine ◽

10.3904/kjm.2012.83.4.520 ◽

2012 ◽

Vol 83 (4) ◽

pp. 520 ◽

Cited By ~ 1

Author(s):

So Ra Lee ◽

Young Min Kim ◽

Ji Yun Jung ◽

Hyung Joon Kim ◽

Doh Hyung Kim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Case Report ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Interstitial Pneumonitis

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Prospective exploratory analysis of the association between genetic polymorphisms and sunitinib toxicity and efficacy in metastatic renal-cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4620 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4620-4620 ◽

Cited By ~ 1

Author(s):

Carlos Alberto Farfan ◽

Juan Sepulveda ◽

Julio Benitez ◽

Guillermo de Velasco ◽

Felipe Villacampa ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Dose Reduction ◽

Median Time ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Preliminary Analysis ◽

Complete Analysis ◽

Increased Risk ◽

Dose Reductions

4620 Background: Sunitinib (SU) is a multi-targeted receptor tyrosine kinase inhibitor treatment that is approved for metastatic renal cell carcinoma (mRCC). However, several patients either do not respond to treatment or they experience significant toxicity.Our study aims to find genetic markers of toxicity and efficacy using a commercially available DNA microarray genotyping system. Methods: 30 patients with newly diagnosed mRCC, from January 2010 to May 2011, were evaluated prospectively at Hospital 12 de Octubre (Madrid, Spain). Pts received SU 50 mg/day, 4 wks on / 2 wks off treatment schedule. A total of 92 of single nucleotide polymorphisms (SNPs) in 34 genes in the pharmacokinetic and pharmacodynamic pathways of drugs were analyzed using Drug inCode pharmacogenetic service. SNPs in candidate genes, together with clinical characteristics were tested univariately for association with the number of days of SU treatment until the first reduction of dose, PFS and OS. Results: Complete analysis was possible in 25 pts. Pts with CYP1A2*1/*1.a low metabolizing genotype, had an increased risk of dose reductions due to toxicity compare to allele *1F (Median time to dose reduction : 2.33 months vs NR; p<0.006). Pts with CYP2C19*1/*1 , wild type genotype, had an increased risk of dose reductions due to toxicity vs. other genotypes (Median time to dose reduction: 2.8 vs 9.73 months; p<0.021). Catechol-O-methyltransferase (COMT) V158M polymorphisms, was associated with PFS and OS (Met/Met carriers median PFS and OS NR; Met/Val pts PFS= 15 months; OS=17.2 months and Val/Val pts PFS=3.3 months; OS= 4.4 months ; p=0.005 for PFS and p=0.003 for OS). Conclusions: This preliminary analysis suggests that CYP1A2 and CYP2C19 SNPs may be associated with toxicity in patients with RCC treated with SU. As CYP1A2 and CYP2C19 activity could be affected by a variety of non-genetic factors, if these is confirmed, it could lead to the necessity of controlling toxic and dietary habits of pts treated with SU. SNPs associated with toxicity and survival in this preliminary analysis are being validated in an independent cohort of RCC treated with SU (García-Donas J, et al. Lancet Oncol 2011).

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